The purposes of this project were: 1) to determine alterations in the metabolism of enkephalins and dynorphins in the limbic-basal ganglia regions after electroconvulsive shock (ECS) or after electrical kindling-induced seizures; 2) to study the possible roles of brain opioid peptides in seizure-induced changes in hippocampal excitability. Previous studies showed that both repeated ECS and electrical kindling to full behavioral convulsions produced striking differences in the hippocampal levels of certain opioid peptides: an increase in enkephalin level, but a drastic decrease in dynorphin level. This project was aimed to determine the underlying mechanism of these differential changes in peptide levels, by measuring the mRNA encoding these two peptides as an index of their biosynthesis. Repeated ECS (once per day for 6 days) or prepyriform cortical kindling to stage 5 convulsions produced a drastic reduction in the abundance of mRNA encoding dynorphin in the hippocampus, while an increase was observed in the hypothalamus and striatum. Thus the changes of mRNA paralleled the alterations of dynorphin levels in these brain regions. These data suggest that ECS- and kindling-induced seizures decrease the biosynthesis of dynorphin in the hippocampus. In contrast, the increase in the hippocampal level of enkephalin after ECS or kindling was not accompanied by an increased amount of mRNA encoding enkephalins. Instead, a large increase of enkephalin mRNA was found in the entorhinal cortex, where the cell bodies of enkephalin-containing neurons projecting to the hippocampus are located. These data-suggest that ECS- or kindling-induced increases in the level of hippocampal enkephalin are mainly derived from the entorhinal cortex through the perforant pathway. Since enkephalins and dynorphins have been shown to be potent in modulating hippocampal excitability, the differential regulation of these two opioid peptides may play important roles in mediating the postictal behaviors.